Whether early exposure to a fat and cholesterol rich diet is necessary to establish normal cholesterol homeostasis or whether such exposures have any 'conditioning' effect on the subsequent response to children and adolescents to the normal 'American diet' are some of the questions that need to be answered in understanding atherogenesis in humans. We plan to compare the concentration and composition of different lipoproteins in the sera of miniature pigs fed high fat-high cholesterol diet during prenatal, neonatal, juvenile and adult periods of life. Simultaneously, the extent of fatty streaking in the aorta and the levels of rate limiting enzymes in the hepatic tissue of the animals will be measured. Very low, low density and fractions (HDLc, HDL2 and HDL3) of high density lipoproteins will be isolated by a combination of ultracentrifugal and electrophoretic methods. Chemical and enzymatic methods will be used to measure the free and esterified cholesterol, triglycerides and phospholipids in each lipoprotein fraction. Apoprotein compositions will be determined by polyacrylamide gel electrophoresis and analytical isoelectrical focusing. HMG-CoA-arductase and 7 alpha-hydroxylase levels in the microsomal portions of hepatic tissue will be determined by sensitive isotopic techniques. This study will demonstrate the development of atherosclerosis at various stages of growth and development as caused by an atherogenic diet and whether such early exposure to fat and cholesterol-rich diet has any conditioning effect on subsequent response to a similar diet at adolescent and adult periods of life. The study will also help to understand the mechanism of regulation of synthesis and absorption of fat and cholesterol, and the mode of transport of these lipids by different lipoproteins, and finally their deposition in the aorta during growth and development. The findings may improve our understanding of the pathogenesis of atherosclerosis during growth in animals and man.